Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

Objective:To establish a rapid and precise dose measurement method with EBT4 film and ensure its measurement accuracy to be within the required range through strict operational procedures for the purpose of addressing the two essential issues of poor measurement accuracy and timeliness of EBT film under FLASH conditions.Methods:After storing under different humidity conditions for a certain period of time, the film was exposed to radiation for analyzing the influence of air humidity on the intrinsic performance of EBT film. By means of repeated scanning operations and the film angle rotation, the influences of repeated scanning and film placement angle were analuzed. Parabolic correction method was used to reduce the spatial position influence during the scanning process. By analying the relationship between net optical density (netOD) and absorbed dose through the comparison of three fitting method, the optimal fitting curve was selected. After irradiation of the same batch of films for 5 min and 24 h, the film doses were calibrated and then compared with ionization chamber-measured result. The rapid and precise film dosimetry method was used to measure both the percentage depth dose from X-rays at ultra-high dose rate and the dose distribution at a depth of 2 cm in water.Results:Air humidity had the greatest influence on the intrinsic performance of EBT film (approximately 20%). The average deviation of repeated scans is within 0.5%. The angle at which the film is placed significantly affected the readouts of the film with the maximum influence approximately 70%. The net optical density combined with polynomial fitting can control the fitting residuals of 1-16 Gy within 3%. The change rate of light channels at 5 min already mostly met the requirements of the rapid mode (< 0.5%). Compared with the measurement result obtained using the reference ionization chamber, the deviations of the 5 min or 24 h dose calibration curves were all within 2%.Conclusions:The EBT4 film can be employed as a precise dosimeter to quickly measure the FLASH radiation dose. Rapid and precise FLASH dose measurements can meet the stringent requirements of both preclinical and clinical FLASH research.

Objective:To analyze the characteristics, diagnosis, and treatment of pulmonary infections related to bronchobiliary fistula (BBF), and to enhance the understanding of this disease.Methods:A total of 33 patients with pulmonary infections related to BBF hospitalized at the Third Affiliated Hospital of Naval Medical University from January 2011 to January 2024 were included in this study. The clinical retrospective case series research method was used to collect and analyze the clinical data of the included patients, including age, clinical manifestations, laboratory tests, imaging studies, bronchoscopy, cholangiography, and treatment.Results:The age of the 33 patients was (51.4±7.9) years. The most common symptoms were coughing and biliary sputum (33/33, 100.0%), followed by fever (23/33, 69.7%). Other common symptoms included chest tightness, dyspnea, chest pain and hemoptysis. Bilirubin tests on sputum were performed in seven cases and on pleural effusions in four cases, and all were positive. Imaging studies revealed pneumonia in all patients, which was adjacent to the diaphragm. All patients had pleural effusion, with additional common findings included subphrenic effusion, liver abscesses, bile duct dilation, and gas in the bile duct. Bronchoscopy was performed on six patients, all of whom exhibited golden yellow biliary secretions. The presence of BBF was confirmed through percutaneous transhepatic cholangiography (6/10), T-tube cholangiography (3/6), and endoscopic retrograde cholangiopancreatography (5/18) in some patients. All patients received anti-infective therapy and supportive treatment. Among the 33 patients, 18(54.5%) cases underwent endoscopic nasobiliary drainage, 12(36.4%) percutaneous transhepatic biliary drainage, 19(57.6%) thoracentesis, 17(51.5%) subphrenic effusion drainage, five (15.2%) liver abscess drainage, 13(39.4%) abdominal paracentesis, and six (18.2%) brochosopic embolization of bronchial fistula. Only three patients underwent surgical intervention when non-surgical treatments failed.Conclusions:The clinical manifestations of pulmonary infections related to BBF are complex. When patients with hepatobiliary diseases present with coughing and biliary sputum, BBF should be highly suspected. Early diagnosis can be achieved through bilirubin testing of sputum or pleural effusion. The main treatments are biliary drainage or percutaneous puncture drainage and other non-surgical treatments. Surgical treatment could be considered only after the failure of non-surgical treatments.

Objective:To analyze the characteristics, diagnosis, and treatment of pulmonary infections related to bronchobiliary fistula (BBF), and to enhance the understanding of this disease.Methods:A total of 33 patients with pulmonary infections related to BBF hospitalized at the Third Affiliated Hospital of Naval Medical University from January 2011 to January 2024 were included in this study. The clinical retrospective case series research method was used to collect and analyze the clinical data of the included patients, including age, clinical manifestations, laboratory tests, imaging studies, bronchoscopy, cholangiography, and treatment.Results:The age of the 33 patients was (51.4±7.9) years. The most common symptoms were coughing and biliary sputum (33/33, 100.0%), followed by fever (23/33, 69.7%). Other common symptoms included chest tightness, dyspnea, chest pain and hemoptysis. Bilirubin tests on sputum were performed in seven cases and on pleural effusions in four cases, and all were positive. Imaging studies revealed pneumonia in all patients, which was adjacent to the diaphragm. All patients had pleural effusion, with additional common findings included subphrenic effusion, liver abscesses, bile duct dilation, and gas in the bile duct. Bronchoscopy was performed on six patients, all of whom exhibited golden yellow biliary secretions. The presence of BBF was confirmed through percutaneous transhepatic cholangiography (6/10), T-tube cholangiography (3/6), and endoscopic retrograde cholangiopancreatography (5/18) in some patients. All patients received anti-infective therapy and supportive treatment. Among the 33 patients, 18(54.5%) cases underwent endoscopic nasobiliary drainage, 12(36.4%) percutaneous transhepatic biliary drainage, 19(57.6%) thoracentesis, 17(51.5%) subphrenic effusion drainage, five (15.2%) liver abscess drainage, 13(39.4%) abdominal paracentesis, and six (18.2%) brochosopic embolization of bronchial fistula. Only three patients underwent surgical intervention when non-surgical treatments failed.Conclusions:The clinical manifestations of pulmonary infections related to BBF are complex. When patients with hepatobiliary diseases present with coughing and biliary sputum, BBF should be highly suspected. Early diagnosis can be achieved through bilirubin testing of sputum or pleural effusion. The main treatments are biliary drainage or percutaneous puncture drainage and other non-surgical treatments. Surgical treatment could be considered only after the failure of non-surgical treatments.

Objective:To compare the efficacy and safety of vildagliptin tablets (the generic drug) manufactured by Qilu Pharmaceutical Co., Ltd. and vildagliptin tablets (the original drug) manufactured by Novartis Pharmaceutical Co., Ltd. in the treatment of type 2 diabetes mellitus (T2DM) in third round of national centralized volume-based procurement.Methods:The study design was a multicenter retrospective cohort study. The study subjects were T2DM patients treated with vildagliptin tablets at the Outpatient Department of Zhuhai People′s Hospital, Zhongshan City People′s Hospital, Jiangmen Central Hospital, and General Hospital of Southern Theater Command of PLA from January 2020 to December 2021. Using the hospital electronic medical record system, medical records in outpatients who met the inclusion criteria were collected, and relevant clinical data were extracted. The patients were divided into generic drug group and original drug group. To exclude the interference of confounding factors, the propensity score matching method was used. The efficacy evaluation index was the magnitude of hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) reductions within one year after administration. Generalized linear regression model was used to analyze the influencing factors for the magnitude of HbA1c and FPG reduction. The safety evaluation index was the incidence of adverse events within one year of drug use.Results:A total of 4 511 patients with T2DM who were treated with vildagliptin tablets were collected from 4 hospitals, including 3 039 in the generic drug group and 1 472 in the original drug group. After treatment, the HbA1c and FPG in patients of the 2 groups decreased compared with those before treatment. The magnitude of HbA1c and FPG reductions in patients of the generic drug group were not significantly different from those in the original drug group [0.50 (0.05, 2.30)% vs. 0.90 (-0.10, 1.70)%, Z=0.235, P=0.814; 0.59 (-0.40, 2.20) mmol/L vs. 1.00 (-0.61, 2.32) mmol/L, Z=0.421, P=0.674]. The results of generalized linear regression model analysis showed that the therapeutic drugs did not affect the magnitude of HbA1c and FPG reductions ( P=0.627, P=0.478). Compared with the original drug group, the incidences of adverse events and hypoglycemia in the generic drug group were not statistically significant [1.6‰ (5/3 039) vs. 2.7‰ (4/1 472), P=0.721; 0.7 ‰ (2/3 039) vs. 0.7 ‰ (1/1 472), P=1.000]. Conclusion:The efficacy and safety of generic vildagliptin tablets manufactured by Qilu Pharmaceutical Co., Ltd. were generally consistent with those of the original drug in the treatment of T2DM.

Objective:To compare the efficacy and safety of vildagliptin tablets (the generic drug) manufactured by Qilu Pharmaceutical Co., Ltd. and vildagliptin tablets (the original drug) manufactured by Novartis Pharmaceutical Co., Ltd. in the treatment of type 2 diabetes mellitus (T2DM) in third round of national centralized volume-based procurement.Methods:The study design was a multicenter retrospective cohort study. The study subjects were T2DM patients treated with vildagliptin tablets at the Outpatient Department of Zhuhai People′s Hospital, Zhongshan City People′s Hospital, Jiangmen Central Hospital, and General Hospital of Southern Theater Command of PLA from January 2020 to December 2021. Using the hospital electronic medical record system, medical records in outpatients who met the inclusion criteria were collected, and relevant clinical data were extracted. The patients were divided into generic drug group and original drug group. To exclude the interference of confounding factors, the propensity score matching method was used. The efficacy evaluation index was the magnitude of hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) reductions within one year after administration. Generalized linear regression model was used to analyze the influencing factors for the magnitude of HbA1c and FPG reduction. The safety evaluation index was the incidence of adverse events within one year of drug use.Results:A total of 4 511 patients with T2DM who were treated with vildagliptin tablets were collected from 4 hospitals, including 3 039 in the generic drug group and 1 472 in the original drug group. After treatment, the HbA1c and FPG in patients of the 2 groups decreased compared with those before treatment. The magnitude of HbA1c and FPG reductions in patients of the generic drug group were not significantly different from those in the original drug group [0.50 (0.05, 2.30)% vs. 0.90 (-0.10, 1.70)%, Z=0.235, P=0.814; 0.59 (-0.40, 2.20) mmol/L vs. 1.00 (-0.61, 2.32) mmol/L, Z=0.421, P=0.674]. The results of generalized linear regression model analysis showed that the therapeutic drugs did not affect the magnitude of HbA1c and FPG reductions ( P=0.627, P=0.478). Compared with the original drug group, the incidences of adverse events and hypoglycemia in the generic drug group were not statistically significant [1.6‰ (5/3 039) vs. 2.7‰ (4/1 472), P=0.721; 0.7 ‰ (2/3 039) vs. 0.7 ‰ (1/1 472), P=1.000]. Conclusion:The efficacy and safety of generic vildagliptin tablets manufactured by Qilu Pharmaceutical Co., Ltd. were generally consistent with those of the original drug in the treatment of T2DM.

[ ABSTRACT] AIM:To explore the effects and mechanism of eleutheroside ( ETS) B or E on the proliferation of HBZY-1 cells treated with high glucose.METHODS:The HBZY-1 cells were cultured under high glucose condition.The 4th generation of HBZY-1 cells was used for determining the optimal cell density, which was consistent with the growth reg-ulation curve of the cells.The cells were divided into 6 groups:low glucose ( LG) group, high glucose ( HG) group, high glucose plus ETS-B/E ( low dose, medium dose and high dose) groups, and high glucose plus losartan ( LTG) group.Af-ter all cells were treated with the corresponding drugs at 24 h, 48 h and 72 h, the inhibitory rate of the proliferation was measured, and the expression of TGF-β1 and PPARγwas detected by immunocytochemistry and Western blotting.RE-SULTS:The best cell density was 2 000 cells/well, which was complied with the basic rules of the cell growth, and high glucose significantly promoted the HBZY-1 cell proliferation.At each time point, the inhibitory effects of ETS-B/E were significantly different between HG group and LTG group on the proliferation of the HBZY-1 cells ( P<0.05) .The expres-sion of TGF-β1 was significantly inhibited, and the expression of PPARγwas significantly promoted by ETS-B/E ( P<0.05).ETS-E showed stronger effect than ETS-B (P<0.05) in a concentration-and time-dependent manner.CONCLU-SION:ETS-B/E significantly inhibits the proliferation of HBZY-1 cells under high glucose condition by decreasing TGF-β1 expression and promoting PPARγexpression.

Objective To analyze the clinical outcome of concurrent ehemo-radiotherapy in stage Ⅳ non-small cell lung cancer(NSCLC).Methods From Jan.1997 to Dec.2006,214 patients with patho logically or cytologically proven stage Ⅳ NSCLC were included in this analysis.Of those patients,98 re ceived radiotherapy concurrently with 3-week cycle chemotherapy(group A),18 received radiotherapy con currently with weekly chemotherapy(group B) ,44 received chemotherapy alone,37 received radiotherapy a lone and 13 received sequential chemo-radiotherapy.The primary tumor was treated by three-dimensional conformal radiotherapy(3DCRT) or conventional radiotherapy with conventional fraefionation or late-course accelerated hyperfraction (LA H RT).Group A received 21-28 days cycle cisplatin-based chemotherapy (cis platin combined with PTX,DTY,NVB or Vp-16) ,and group B received weekly DDP combined with PTX or topteeon for 4-6 weeks.Results The follow-up rate was 99%.The 1-and 2-year overall survival rates of group A,group B,chemotherapy alone,radiotherapy alone and sequential chemo-radiotherapy were 41% and 11% ,16% and 0,31% and 7% ,34% and 10% ,26% and 3% ,respectively(x2 = 11.18,P=0.025).The patients with concurrent 3DCRT,LAHRT and radiotherapy dose≥70 Gy had better survival in group A than those in chemotherapy alone group.Patients who received≥2 cycles chemotherapy with concurrent radio therapy had longer survival time than those who had ≥2 cycles chemotherapy alone. Conclusions Con current chemotherapy and 3DCRT,LAHRT with the dose ≥70 Gy can improve the overall survival of patients with stage Ⅳ non-small cell lung cancer.